Effect of Low-fat Diet on the Pharmacokinetics of Pyrotinib in Healthy Participants

A Randomized, Open, Single-dose, Two-cycle, Double-sequence, Crossover Study to Investigate the Effects of a Low-fat Diet On the Pharmacokinetics of Healthy Chinese Adult Participants After Oral Administration of Pyrotinib Maleate Tablets

The primary objective of the study is to evaluate the effect of low-fat diet on pharmacokinetics of healthy Chinese adult participants after oral administration of pyrotinib maleate tablets.

The secondary objective of the study is to evaluate the safety of single dose of pyrotinib orally in healthy participants.

Study Overview

• Status: Unknown
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: pyrotinib maleate fasted in P1, low-fat diet in P2; Drug: pyrotinib maleate low-fat diet in P1, fasted in P2

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuya Wang, Ph.D.; Phone Number: 86-13918749176; Email: wangyuya@hrglobe.cn
• Study Contact Backup: Name: Chao Lu, M.M.; Phone Number: 86-18005693201; Email: 765385306@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions;
2. Ability to complete the study as required by the protocol;
3. Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
4. Have no fertility plan and agree to adopt effective contraceptive measures within 2 weeks before the first study drug administration and up to 3 months after the last study drug administration. Negative pregnancy test for women of child-bearing age before the first study drug administration;
5. Male body weight ≥ 50kg, female body weight ≥ 45kg, and body mass index (BMI) within the range of 19 ~ 26 kg/m^2 (including 19 and 26);
6. During screening period, the comprehensive physical examination (vital signs and physical examination), routine laboratory examination (blood routine, urine routine, blood biochemistry, coagulation,etc), 12-lead electrocardiogram (ECG), chest X-ray, cardiac ultrasound, B ultrasound and other examination results must be within the normal range, or judged to be "no clinical significance (NCS)" if beyond the normal range;

Exclusion Criteria:

1. Blood donation within 3 months before the first drug administration and blood loss greater than 400 mL, or receiving blood transfusion;
2. Allergic constitution, including those with severe drug allergies or a history of drug allergies, or known allergy to the research drug;
3. History of drug use, or drug abuse screening positive; history of drug abuse within the past five years or have used drugs 3 months before the test;
4. Alcoholic or often drinkers (the average drinking amount is more than 14 units a week: 1 unit= 285 ml beer or 45 ml spirits or 100 ml wine; ≥5 cigarettes per day) and can't quit smoking and alcohol during the study; alcohol test positive;
5. The 12-lead ECG with female QTcF > 470ms or male QTcF > 450ms;
6. Left ventricular ejection fraction (LVEF) <50% by echocardiography;
7. A clear medical history of important primary organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal system.
8. Those who have undergone any surgery within 6 months before screening;
9. Those who have taken hepatotoxic drugs (such as dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for a long time within the 6 months before screening;
10. Those who have taken any research drugs within 3 months before the first drug administration;
11. Use any drugs that changes liver enzyme activity within 4 weeks before the first drug administration;
12. Use any prescription or over-the-counter drug, any vitamin product, health supplement or herbal medicine within 2 weeks prior to first drug administration;
13. Abnormal clinical laboratory tests and clinical significance judged by the investigator or other clinical findings showing the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases;
14. HCV antibody positive, HIV antibody positive, HBsAg positive, and syphilis antibody positive;
15. Consumption of grapefruit or grapefruit-containing products, foods or beverages containing caffeine, xanthine, or alcohol within 48 hours before the first drug administration; strenuous exercise or other factors that effect on drug absorption, distribution, metabolism and excretion;
16. Have special requirements on diet and cannot comply with the diet and corresponding regulations provided by the test;
17. History of dizzy needles or blood dizziness; difficulty in venous blood collection or inability to tolerate venipuncture;
18. lactating women;
19. Other factors that are not suitable for participating in the study, as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: pyrotinib maleate fasted in P1, low-fat diet in P2; pyrotinib maleate administration in fasted condition in period 1, pyrotinib maleate administration after low-fat diet in period 2
Experimental: B	Drug: pyrotinib maleate low-fat diet in P1, fasted in P2; pyrotinib maleate administration after low-fat diet in period 1, pyrotinib maleate administration in fasted condition in period 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Cmax of pyrotinib	Peak Plasma Concentration (Cmax) of pyrotinib	through study completion, an average of 28 days
Pharmacokinetics parameter: AUC of pyrotinib	Area under the plasma concentration versus time curve (AUC) of pyrotinib	through study completion, an average of 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameter: Tmax of pyrotinib	Time of maximum observed concentration (Tmax) of pyrotinib	through study completion, an average of 28 days
Pharmacokinetics parameter: T1/2 of pyrotinib	Half time (T1/2) of pyrotinib	through study completion, an average of 28 days
Pharmacokinetics parameter: CL/F of pyrotinib	Total body clearance for extravascular administration (CL/F) of pyrotinib	through study completion, an average of 28 days
Pharmacokinetics parameter: Vz/F of pyrotinib	Volume of distribution (Vz/F) of pyrotinib	through study completion, an average of 28 days
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	An adverse event is any untoward medical occurrence in a patient or clinical study participant	through study completion, an average of 28 days

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: BLTN-If

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No